THYROID MALIGNANCY MANAGEMENT

Robert Tasevski

AST 2

Advanced Trainee Seminar Program

17th April 2004

OVERVIEW

1. Introduction

2. Classification of Thyroid Cancer

3. Epidemiology and Aetiology

4. Diagnosis

5. Papillary Carcinoma

6. Follicular carcinoma

7. Adjuvant therapy for Differentiated Thyroid Cancer

8. Hurthle cell Carcinoma

9. Anaplastic Carcinoma

10. Medullary thyroid Cancer

11. Thyroid Lymphoma

12. Metastatic Carcinoma to the Thyroid Gland

INTRODUCTION

• Thyroid cancer is rare (3.7-4.7 per 100,000 population).

• Accounts for less than 1% of all malignancies and 0.5% of all cancer deaths.

• Thyroid cancer constitutes an extremely heterogeneous group of tumours, with a wide spectrum of biological behaviour.

• In most instances if treated appropriately there is a high survival rate.

• In view of the low incidence of thyroid cancer and the generallygood prognosis, there is a lack of long-term follow-up studies and randomised, prospective trials comparing various treatments.

• Optimal management remains controversial for many of these tumours and is often based on retrospective studies.

CLASSIFICATION OF THYROID CANCER

TYPE INCIDENCE

• Differentiated thyroid carcinoma (DTC)

• Papillary carcinoma (PTC) 80%

• Follicular carcinoma (FTC) 10%

• Hurthle cell carcinoma 3%

• Anaplastic carcinoma 1%

• Medullary thyroid carcinoma (MTC) 5%

• Lymphoma 1%

• Metastatic carcinoma <1%

EPIDEMIOLOGY & AETIOLOGY

• Affects more women than men (2:1).

• Median age of onset is between the 4th and 5th decades of life.

• Aetiology of thyroid carcinoma is multifactorial with environmental and inherited features.

• Exposure to radiation (e.g. previous neck irradiation), especially in children, is a major risk factor. Approximately 85% of such irradiation-induced tumours are papillary.

• Therapeutic doses of 131I, such as those used to treat hyperthyroidism, have not been shown to increase risk of subsequent tumour occurrence.

• High dietary iodine intake increases the incidence of papillary carcinoma, whereas low iodine content is goitrogenic and may lead to follicular or anaplastic carcinoma.

Role of Molecular Genetic Changes

• Molecular genetic studies have identified characteristic abnormalities in many thyroid cancers.

• The RET proto-oncogene plays a significant role in the development of papillary thyroid cancer and familial medullary thyroid cancer.

• The RET gene is located on chromosome 10 and encodes for a tyrosine kinase receptor on the cytoplasmic membrane.

• Rearrangement of RET occurs in PTC (leading to increased transcription).

• Point mutations involving RET have been demonstrated in familialMTC, MEN 2A, and MEN 2B.

• Point mutations in the ras oncogenes have been demonstrated in follicular adenomas, MNG, as well as follicular carcinomas.

• A mutated p53 gene is found in most anaplastic thyroid cancers. This is a tumour suppressor gene encoding a protein (p53) that acts as a transcriptional regulator and maintains genomic integrity.

• Certain familial cancer syndromes, eg. FAP, Cowden syndrome, areassociated with an increased occurrence of DTC.

DIAGNOSIS

• Patients with thyroid carcinoma usually present with a solitary thyroid nodule.

• Palpable thyroid nodules are common, being present in about 4% of the population.

• The vast majority are benign.

• A combination of careful clinical assessment and investigations will aid the distinction between benign and malignant nodules.

History

• Age

• Sex

• Family history of thyroid cancer

• History of previous head and neck irradiation

• History of the thyroid nodule• Onset

• Growth

• Pain

• Hoarseness

• Dysphagia

• Dyspnoea

• Other neck/supraclavicular lumps

Physical Examination

• Characterise the thyroid nodule• Size

• Shape

• Surface

• Consistency

• Fluctuance

• Tenderness

• Fixation of the nodule to adjacent structures (eg. strap muscles, trachea)

• Presence of diffusely multinodular goitre

• Palpable cervical lymphadenopathy

• Assess thyroid status

Fine-Needle Aspiration Cytology (FNAC)

• The procedure of choice in evaluating thyroid nodules• Fast

• Few risks

• Technically simple

• Minimally invasive

• Specific and sensitive

• Sensitivity: 68%-98%

Specificity: 56%-100%,

Overall sensitivity and specificity depends on the adequacy of the samples and experience of the cytopathologist.

• False-positive: 1%

False-negative: 5%

When FNAC is used in experienced hands.

FNAC Results

• On the basis of FNAC results, thyroid nodules can be categorized into the following groups:

• Benign 65%

• Indeterminate/Suspicious 15%

• Malignant 5%

• Nondiagnostic 15%

• Nondiagnostic category is usually due to an inadequate specimen.Repeat FNAC, with ultrasound guidance if necessary, should be performed.

• Papillary, medullary, and anaplastic carcinomas can be readily diagnosed on FNAC.

• Follicular adenoma and follicular carcinoma are indistinguishable cytologically (vascular or capsular invasion must be demonstrated histologically for malignancy) and hence are grouped in the indeterminate/suspicious category.

Indeterminate/Suspicious Lesions

• This cytologic category remains a challenge (for pathologists and surgeons alike).

• Since approximately 20%of these lesions ultimately prove to be malignant, surgical intervention is usually recommended.

• Intraoperative frozen section analysis of most follicular and Hurthle cell neoplasms is unlikey to yield additional useful information due to the inherent insensitivity of the frozen section in demonstrating capsular or vascular invasion.

• There is a clear need to develop ancillary tests in order to avoid unnecessary surgery.

• Potential markers of thyroid malignancy that hold promise as adjuncts to FNAC are currently being investigated.

• Galectin-3: Acts as a cell death suppressor by interfering with apoptosis. Expressed by only a small number (15%) of benign follicular lesions compared to most (87%) of FTCs.

• Thyroid Peroxidase (TPO): Present in all thyroid follicular cells and plays central role in thyroid hormone synthesis. Decreased levels of TPO-specific mRNA have been documented in thyroid cancer.

• Hopefully combining these molecular and immunohistochemical assays with the cytologic evaluation of FNA samples will solve the clinical problem of the suspicious thyroid lesion in the near future.

Other Investigations

• Thyroid Function Tests: To check the thyroid status. Most patients with thyroid cancer are euthyroid.

• Serum Calcitonin Level: Not routinely performed, but should be obtained in patients with a family history of MTC or MEN 2 and where FNAC demonstrates MTC to be present.

• Thyroid Ultrasonography: Helpful for detecting nonpalpable nodules and for differentiating solid from cystic nodules.

• CT and MRI: Usually unnecessary except for large or retrosternal lesions and for assessing suspected invasion into surrounding structures.

• Thyroid Isotope Scanning: Should be reserved for patients with thyrotoxicosis and nodules of indeterminate cytological status.

Algorithm for Evaluation of the Thyroid Nodule

PAPILLARY CARCINOMA

• Commonest thyroid malignancy (80%)

• 2:1 female-to-male ratio

• Mean age at presentation is 30-40 years.

• Increased incidence in iodine-rich areas.

• Predominant thyroid cancer in people previously exposed to neck irradiation.

• Rare familial form of the disease has been described.

Pathology

• Frequently multifocal (30%-87.5%).

• Propensity for lymphatic spread within the thyroid and to local lymph nodes (paratracheal and cervical chain).

• Blood-borne spread is a late feature.

• Microscopically: cuboidal cells with pale abundant cytoplasm, crowded nuclei, and intranuclear cytoplasmic inclusions (Orphan Annie cells)

• Macroscopically can be divided into 3 main types based on size and extent:

Minimal: Also called papillary microcarcinoma. Tumours 1cm or less in size with no evidence of local invasion through the thyroid capsule and no lymph node metastases. Not clinically obvious and found incidentally at surgery/autopsy. Present in 6-13% thyroid glands at autopsy (cause of death other than thyroid disease).

Intrathyroidal: Greater than 1cm with no evidence of extrathyroidal invasion.

Extrathyroidal: Locally advanced with invasion through the thyroid capsule into adjacent structures.

• Follicular, encapsulated, tall-cell and other variants of papillary thyroid carcinoma have been described.

Clinical Presentation

• Most patients present with a slow-growing, painless mass in the neck.

• Involvement of adjacent structures by advanced locally invasive disease may cause hoarseness, dyspnoea or dysphagia.

• Enlarged cervical lymph nodes may be present and are most commonly encountered in younger patients.

• Nodal involvement may be more apparent than the primary lesion (lateral aberrant thyroid).

• Only about 35% of patients have clinically detectable cervical or mediastinal lymph nodes at initial surgery, although microscopic lymph node metastases are seen in 80%.

• Evidence of distant metastases are uncommon at initial presentation (although up to 20% of patients ultimately develop distant spread).

Prognostic Factors & Staging

• The development of a universally satisfactory staging system to guide prognosis and treatment has been a challenge.

• Various prognostic scoring systems have been developed which separate patients into high and low risk groups for risk of recurrence and long-term survival.

AMES: Age, Metastases, Extent and Size of tumour

AGES: Age, histological Grade, Extent and Size of tumour

MACIS: Metastases, Age, Completeness of resection, Invasion, Size

• Age at diagnosis is an important prognostic factor, with youngerpatients (<45 y.o.) having a more favourable outlook.

• Most patients fit into the low risk group with an excellent long-term prognosis

Surgical Treatment of PTC

• No prospective clinical trials have been performed to determine the ideal treatment.

• Total thyroidectomy is appropriate if:• Size > 1cm

• Extrathyroid invasion

• Metastases

• History of head/neck irradiation

• The arguments for total thyroidectomy include:• Treats multifocal disease

• Decreases local recurrence

• Reduces risk of anaplasia in any residual tissue

• Facilitates treatment with 131I

• Permits post-op monitoring with thyroglobulin concentration

• Total thyroidectomy has not been demonstrated to have better survival rates than near-total throidectomy.

Surgical Treatment of PTC

• Unilateral thyroid lobectomy and isthmusectomy is adequate for minimal (< 1cm) lesions and the rare encapsulated papillary cancers, as they generally have an excellent prognosis.

• The arguments for unilateral surgery include lower risk of hypoparathyroidism and RLN injury .

• In experienced hands <2% incidence of permanent hypoparathyroidism or nerve injury after total thyroidectomy.

Surgical Treatment of PTC

• Proper management of occult lymph node metastases also remains controversial.

• In the absence of obvious nodal involvement, it is adequate to perform a central neck node dissection (pretracheal and paratracheal lymph nodes). Some argue that this is unnecessary.

• Those with lateral neck nodal disease should have pre-op FNAC or intra-op frozen section to confirm metastases.

• Confirmed lateral neck disease should be treated with a modified radical neck dissection. This operation spares the IJV, SCM and accessory nerve.

FOLLICULAR CARCINOMA

• Less common (10%)

• 3:1 female-to-male ratio.

• Presents in an older age group, with mean age 50 yrs.

• Higher incidence in iodine-deficient areas.

• Rarely occurs in familial form.

Pathology

• Usually solitary

• Invariably encapsulated

• Vascular invasion and haematogenous spread to bone, lung, and liver are common.

• Lymphatic spread is usually a late phenomenon.

• Microscopically: most follicular carcinomas are composed of fairly uniform cells forming small follicles containing colloid, quite reminiscent of normal thyroid. In other cases, follicular differentiation may be less apparent.

• Classified into 2 types according to histopathological features:

Minimally Invasive: Invasion into but not through the thyroid capsule (previously reported as atypical adenomas, but should regarded as low-grade carcinomas).

Frankly Invasive: Vascular invasion or tumour invasion through the thyroid capsule.

Clinical Presentation

• Usually present as a discrete solitary thyroid nodule increasing in size.

• Occasional history of long-standing goitre.

• When haemorrhage into the nodule has occurred pain may be a feature, but usually they are painless.

• Cervical lymphadenopathy is uncommon at initial presentation.

• Distant metastases may already be present at the time of diagnosis, with bone, lung or liver involvement.

• Rarely, patient may be thyrotoxic as 1% of these tumours are hyperfunctioning.

Surgical Treatment of FTC

• Follicular lesions diagnosed on FNAC are treated by total thyroid lobectomy, isthmusectomy and removal of the pyramidal lobe.

• As intra-operative frozen section is usually unhelpful, definitive histology is awaited:

• Minimally invasive FTC ® unilateral procedure is adequate

• Frankly invasive FTC ® total thyroidectomy is required

• Completion thyroidectomy should be performed either within a few days of the initial lobectomy or after a period of 3-4 months.

• A decision to proceed directly to a total thyroidectomy can sometimes be made at the time of surgery on the basis of the macroscopic appearance of the lesion, especially when tumour size > 4cm (cancer risk about 50%).

• Lymph node dissection is not routinely performed for FTC, but therapeutic neck dissection is recommended as for PTC.

ADJUVANT THERAPY FOR DIFFERENTIATED THYROID CANCER

After initial surgery, adjuvant therapy should prolong survival and

improve quality of life by elimination of microscopic residual or

metastatic disease.

1. Thyroxine (T4)

• Patients who have undergone total thyroidectomy require thyroid hormone replacement to prevent hypothyroidism.

• The dose of T4 is titrated to suppress TSH levels to keep to a minimum stimulation of tumour growth.

• Overly aggressive TSH-suppressive T4 therapy can cause acceleration of osteoporosis, provocation of AF, and cardiac hypertrophy and dysfunction.

2. Radioactive Iodine (131I)

• Approximately 6 weeks post total thyroidectomy, patients undergoradioiodine ablation of residual thyroid tissue. The rationale for this is:

1. To destroy any residual microscopic foci of disease

2. To increase specificity of subsequent 131I scanning for detection of recurrent or metastatic disease by elimination of uptake by residual normal thyroid tissue

3. To improve the value of measurements of serum thyroglobulin as a serum marker derived only from malignant thyroid cells

• The scans are repeated at 6-monthly intervals, and repeated therapeutic doses of 131I are given as necessary until all residual uptake is ablated.

• Once stable and disease free, patients are followed-up clinically and with measurement of serum thyroglobulin.

• Some thyroid cancers cannot concentrate iodine:• 20% PTC in >50 y.o.

• Hurthle cell carcinoma

PREPARATION FOR RADIOIODINE SCANS

• Successful radioiodine scanning requires serum TSH to be above acertain level (>25 IU/mL) in order to stimulate iodine uptake by the remaining thyroid tissue.

• Post thyroidectomy there are a number of ways to prepare patients for radioiodine scanning:

1. Withold T4 replacement therapy for 3-6 weeks after surgery and accept the iatrogenic hypothyroidism provided the patient tolerates it.

2. Discharge patient on T3 rather than T4. Because T4 has a 7-day half-life it must be witheld for 4-5 weeks to allow TSH concentrations to rise. T3 has a more rapid metabolic clearance than T4, and can be given to minimise the effects of hypothyroidism until 2 weeks before radioiodine scanning.

3. T4 can be continued and the patient administered exogenous humanrecombinant TSH (daily dose for 2 days prior to the radioiodine scan).

• Patients should avoid foods with high iodine content for at least 2 weeks before the scan.

Recurrence Rates in PTC

Thyroglobulin as a Tumour Marker

• Thyroglobulin is the major constituent of colloid and precursor of thyroid hormones.

• Measurement of serum thyroglobulin concentration is a sensitive indicator of residual or recurrent differentiated thyroid cancerafter total thyroidectomy.

• Measurement can be performed routinely at each follow-up visit.

• Has markedly reduced the need for routine serial 131I scanning.

• Unfortunately, thyroglobulin autoantibodies, present in 25% of patients with thyroid cancer, can interfere with measurement and falsely lower thyroglobulin concentrations. Hence, there ispotential to underestimate the likelihood of recurrent/metastatic disease.

HURTHLE CELL CARCINOMA

• 3% of thyroid malignancies.

• Variant of follicular cell neoplasms.

• Derived from the oxyphilic cells of the thyroid gland. Tumours contain cells with eosinophilic granular cytoplasm and large clear nuclei.

• Possess TSH receptors and produce thyroglobulin, but only 10% trap radioiodine.

• Differ from follicular carcinoma in that they are more often multifocal and bilateral, and more likely to metastasise to local nodes (25%).

• Hurthle cell neoplasms are diagnosed by FNAC, of which 20% are malignant.

• More aggressive compared to other differentiated thyroid cancers, with higher rate of metastases at presentation, and overall lower survival.

Treatment of Hurthle Cell Carcinoma

• Hurthle cell adenoma and carcinoma cannot be differentiated on FNAC.

• Thyroid lobectomy, isthmusectomy and pyramidal lobe resection issufficient for unilateral Hurthle cell adenomas.

• If Hurthle cell carcinoma is confirmed on intra-operative frozen section (rarely) or definitive histology (usually), then total thyroidectomy should be performed.

• Routine central neck node dissection should be performed.

• Modified radical neck dissection should be performed when the lateral neck nodes are involved.

• TSH-suppressive T4 therapy is recommended post-op.

• 131I scanning and ablation should be considered to ablate any residual normal thyroid tissue and occasionally tumour, since there is no other good therapy.

• 99mTc-sestamibi scanning is useful for detecting persistent local or metastatic disease.

ANAPLASTIC CARCINOMA

• One of the most aggressive malignancies, with few patients surviving 6 months beyond diagnosis.

• 1.5:1 female-to-male ratio

• Peak incidence between 60-70 yrs of age.

• Higher incidence in endemic goitrous areas.

• Most anaplastic carcinomas arise from differentiated thyroid cancers

• Rare (1% of thyroid cancers) and the proportion has steadily decreased over the last few decades. Reasons for the decline include:

1. Many previously described cases of anaplastic carcinoma were actually cases of thyroid lymphoma or undifferentiated medullary thyroid cancer.

2. Use of iodine prophylaxis in iodine-deficient areas.

3. Increased surgical resection for a variety of thyroid conditions over the last few decades has eliminated that transformation of differentiated thyroid carcinoma into anaplastic carcinoma.

Pathology

• Macroscopically: Unencapsulated, tan-white, fleshy tumours with direct extension into the surrounding soft tissues of the neck, with regions of necrosis and haemorrhage.

• Microscopically: Sheets of cells with marked heterogeneity. Spindle-shaped, polygonal, and large multinucleated cells are seen. Foci of more differentiated cells may be seen, either follicular or papillary in pattern.

• Rapidly infiltrates local structures and metastasises via the blood stream and lymphatics.

Clinical Presentation

• The diagnosis is usually suspected on clinical assessment.

• Typically elderly females.

• Lump in the neck that has been present for some time before rapidly enlarging and becoming painful.

• Associated symptoms such as dysphonia, dysphagia and dyspnoea are common.

• The tumour is hard and may be fixed to surrounding structures or may be ulcerated.

• Lymph nodes are usually palpable at presentation (40%)

• Evidence of metastatic disease may also be present (50% at presentation but increases to 75% during course of illness). Common sites are lung, bone, and brain.

Diagnosis

• FNAC: Thyroid mass or lymph node metastases.Reveals characteristic giant & multinucleated cells.Accurate in 90% of cases.

• Incisional biopsy to confirm the diagnosis is rarely necessary.

• CT scan of the neck and chest is useful in defining the local extent of the disease and demonstrating distant metastases.

Treatment of Anaplastic Carcinoma

• All treatment forms have been disappointing.

• Multimodality therapy is the treatment of choice, with surgery being followed by radiotherapy and sometimes chemotherapy.

• Surgical excision is justified if cervical and mediastinal disease can be resected with limited morbidity.

• In a few published series, grossly complete tumour resection when followed by adjuvant radiotherapy and chemotherapy has yielded a small survival benefit, when the tumour seems confined to the neck (75-80% survival at 2 yrs)

• For tumours that cannot be completely resected, palliative debulking and adjuvant radiotherapy, whilst improving local control, do not prolong survival.

• At the least, surgery should aim to relieve an obstructed airway by excision of the isthmus.

• Although 40% of patients respond initially to external beam radiotherapy, most have local recurrence.

• Single-drug chemotherapy does not improve survival or local disease control, although 20% have some response in distant metastases.

• Doxorubicin is often combined with radiotherapy as a radiosensitiser.

• Combination chemotherapy has not shown improved control of distant disease or improved survival.

• Paclitaxel has recently been tested in newly diagnosed patients, and could provide some palliative benefit.

MEDULLARY THYROID CANCER

• 5% of all thyroid cancers.

• Arise from the neuroectodermal derived parafollicular or C-cells of the thyroid. These cells are concentrated mainly in the superior poles laterally.

• C-cells secrete calcitonin.

• The disease is sporadic in 80% of cases and familial in 20%.

• The familial syndromes are inherited in an autosomal dominant manner and consist of:

• MEN 2A: MTC, hyperparathyroidism, phaeochromocytoma

• MEN 2B: MTC, phaeochromcytoma, ganglioneuromatosis, Marfan’s

• Familial medullary thyroid cancer: MTC alone

Pathology

• Occurs in the upper two-thirds of the thyroid.

• Sporadic form: Unilateral

Familial form: Multicentric & bilateral

• Microscopically composed of sheets of inflitrating neoplastic cells separated by collagen and amyloid. Marked heterogeneity; cells may be polygonal or spindle-shaped.

• C-cell hyperplasia is a premalignant precursor of MTC.

• Spreads initially to local lymph nodes in the neck and superior mediastinum.

• Distant blood-borne metastases to liver, lungs and bone arise later in the disease.

• Synthesise and secrete calcitonin (helpful biochemical and histological marker), CEA, and calcitonin gene-related peptide (CGRP).

Clinical Presentation

• Presents with a neck mass that may be associated with palpable cervical lymphadenopathy (15-20%).

• Local invasion may produce symptoms of dysphagia, dyspnoea and dysphonia.

• 1.5:1 female-to-male ratio.

• Sporadic disease has peak incidence at 40-50 years of age.

Familial disease is seen at a younger age.

• Secrete a range of hormones and peptides including calcitonin, prostaglandins, serotonin, ACTH, CEA, and CGRP. Oversecretion in advanced disease can lead to unexplained diarrhoea, facial flushing, and symptoms of Cushing’s syndrome.

• In MEN 2, renal stones may occur in primary hyperparathyroidism, and hypertension occurs in those with phaeochromocytoma.

Diagnosis

• Clinical assessment: Attention to family history is important.

• FNAC: Confirms the diagnosis.

• Serum calcitonin level: Raised. Measure when there is a high index of suspicion.

• To help distinguish sporadic from familial disease, all new patients with MTC should be screened for RET point mutations.

• Screen for phaeochromocytoma by measuring 24-hour urinary levels of vanillylmandelic acid (VMA), catecholamines, and metanephrine. Operating on a patient with undiagnosed phaeochromocytoma can result in hypertensive crisis and death.

• Screen for primary hyperparathyroidism by measuring serum calcium level.

Surgical Treatment

• Total thyroidectomy should be performed to adequately treat multicentric and bilateral disease and because of its more aggressive course.

• A central neck node dissection should always be performed• carotid sheath to trachea including paratracheal nodes, from the level of thyroid

cartrilage to the upper mediastinum, including thymectomy as necessary

• In patients with palpable cervical nodes or involved central neck nodes:• In sporadic disease ipsilateral modified radical neck dissection is recommended

• In familial disease bilateral modified radical neck dissection is recommended

• When primary tumour is greater than 2cm, ipsilateral prophylactic

modified radical neck dissection is recommended.

• In MEN 2A and MEN 2B:• Phaeochromocytomas should be operated on first, before thyroiodectomy is

performed.

• In patients with hypercalcaemia at the time of thyroidectomy, the parathyroid glands should be identified and, when abnormal, selectively removed.

Adjuvant Therapy

• Thyroid hormone replacement is commenced for treatment of iatrogenic hypothyroidism, with maintenance of normal TSH as there is no benefit from TSH suppression.

• No role for radioiodine treatment.

• External beam radiotherapy should be considered for patients at high risk of regional recurrence (microscopic residual disease, extraglandular invasion, lymph node metastases), even after optimum surgical treatment. Retrospective studies have shown benefit with a decrease in locoregional relapse.

• No effective chemotherapy regime.

Post-Operative Follow-Up

• Regular clinical and biochemical follow-up.

• Serum calcitonin and CEA levels should be monitored regularly.• When increased concentrations of these agents persist after thyroidectomy or

develop subsequently this may signify persistent or recurrent disease, respectively.

• Raised levels are a concern signaling the need for evaluation.

• The investigative tools available include:• Ultrasound of the neck

• CT scan of neck, chest, liver

• MRI of neck and liver

• Nuclear imaging studies with MIBG, DMSA and 99mTc-sestamibi

• PET scanning

• Selective venous catheterisation with calcitonin assay

• Laparoscopy for liver metastases

• A proportion of these patients can be helped with further surgery, but the benefits of radical reoperative surgery remain controversial.

Prognosis

• The presence of distant metastases and lymph node positivity aremajor prognostic factors.

• Overall 10-year survival figures of 90% have been reported, but when lymph node metastasis is present this is reduced to 45%.

• Disease type also influences survival. It is best in familial non-MEN MTC, followed by MEN 2A, then those with sporadic disease, and worst in patients with MEN 2B.

• Prophylactic thyroidectomy is recommended for at-risk family members who are identified as carriers of a familial RET mutation.

• Performing thyroidectomy early, after the age of 5 yrs, at the C-cell hyperplasia stage or before, will prevent MTC.

THYROID LYMPHOMA

• 1% of thyroid cancers.

• Primarily a disease of elderly women.

• Usually non-Hodgkin’s B-cell type.

• Although the disease can arise as part of a generalised lymphomatous condition, most thyroid lymphomas develop in patients with chronic lymphocytic (Hashimoto’s) thyroiditis.

• Usually present with symptoms similar to those of anaplastic carcinoma, although the rapidly enlarging mass is usually painless.

• There may be a history of goitre, and some patients will be clinically hypothyroid or already receiving T4.

Treatment of Thyroid Lymphoma

• Diagnosis is usually suggested by FNAC, although core or open biopsy is usually required for definitive diagnosis.

• Chemotherapy and radiotherapy are the main treatment modalities.

• Chemotherapy is of most value for extrathyroidal and disseminated disease.

• Surgery has a role to free the trachea when there is impending obstruction.

• Debulking surgery has not been shown to increase remission rates, although there are no prospective studies.

• 5-year survival of 85% has been reported, but prognosis is significantly affected by the histological grade and presence oflocally extensive or disseminated disease.

METASTATIC CARCINOMA TO THE THYROID GLAND

• The thyroid gland, rarely, is the site of metastatic spread fromother cancers.

• Renal cell carcinoma is the most common metastatic tumour to the thyroid.

• Others include breast, lung, and melanoma.

• History and clinical examination often suggest the source.

• Confirmation is usually obtained by FNAC.

• Resection of the thyroid, usually lobectomy, is indicated if theprimary disease is otherwise well controlled.

SENTINEL LYMPH NODE BIOPSY IN THYROID MALIGNANCIES

• Although sentinel lymph node biopsy (SLNB) is now firmly established as a valuable technique in the management of melanoma and breast cancer, the clinical relevance of identifying regional node metastases by this technique in thyroid cancer remains to be determined.

• It has been demonstrated that SLNB is indeed an accurate technique for obtaining information about cervical lymph node involvement in patients with thyroid cancer.

• The advantages of SLNB in melanoma and breast cancer are:1. Axillary and groin lymph node dissections are potentially morbid procedures

(lymphoedema, nerve injury, shoulder stiffness) and require a substantial skin incision.

2. Information about lymph node status is a significant prognostic factor determining survival and guiding further management.

• Neither of these criteria is met when SLNB is applied to PTC:1. Central neck node dissection is carried out at thyroidectomy through

the same incision and does not necessarily increase the complication risk.

2. Cervical lymph node involvement has never been demonstrated to be a prognostic factor in relation to the survival of patients with PTC, other than in a select group with advanced disease.

• SLNB in PTC may have a place in guiding the surgeon as to the extent of dissection to be undertaken by identifying the small percentage of patients in which the SLN is located in the lateral neck compartment rather than central compartment.

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